ENOS, physiological functions

Several epidemiological studies have linked a protective effect against cardiovascular diseases and regular consumption of either red wine [7, 8, 98] or polyphenol-rich sources such as green tea [14,15,99], cocoa, or chocolate [16,17]. Since many cardiovascular diseases are associated with an impaired endothelial function, the evaluation of the endothelial function is of great importance. In humans, the endothelial function is often assessed by the flow-mediated dilatation (FMD). For this purpose, reactive hyperemia is induced after a transient ischemia in the upper arm using an inflatable cuff like that used for the measurement of blood pressure, while the diameter of the brachial artery is monitored continuously at the elbow level by ultrasound. The cuff is inflated tmtil the occlusion of the brachial artery, which is maintained for 5 min before the blood flow is released. The reperfusion then induces an endothelium-dependent dilatation of the brachial artery due to the increased shear stress, the most important physiological activator of eNOS. Impaired endothelial function, assessed by FMD, has been reported as an independent predictor of cardiovascular outcome in subjects with cardiovascular risk factors or established cardiovascular diseases [18]. 

Under physiologic conditions, unlike eNOS and nNOS, iNOS is not expressed constitutively in mammalian cells, but rather is induced by pro-inflammatory stimuli, such as bacterial lipopolysaccharide (LPS), or the cytokines TNF-a, ILip, or interferon-y (IFN-y), individually, or in combination. Inducible NOS possesses tightly bound calmodulin in a non-covalent manner and is calcium independent. Therefore, once expressed, iNOS continues to synthesize NO- in large amounts for a prolonged period of time. Inducible NOS activity is regulated by protein expression rather than functional modulation (Lee et al. 2003). 

---